Altered Prefrontal Glutamate–Glutamine–γ-Aminobutyric Acid Levels and Relation to Low Cognitive Performance and Depressive Symptoms in Type 1 Diabetes Mellitus

Abstract

The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system-related changes in patients with adult type 1 diabetes.

Prevalence of depressive symptoms and diagnosed depression among subjects with longstanding type 1 diabetes and no serious chronic complications, hospitalized due to inadequate metabolic control of diabetes

“…Rapid fluctuations of glucose levels, chronic hyperglycemia, acute hypo or hyperglycemia are associated with low grade inflammation, elevated cytokine levels and oxidative stress [14]. High variability of glucose levels may influence the function of brain areas responsible for mood and cognition and therefore precipitate depressive symptoms [15]. To emphasize, in our study, none of participants had symptoms of hypoglycemia or acute hyperglycemia during answering the questionnaire.…”

Examination of the Synergistic Relationship of Diabetes and Depression

“…There is growing evidence that suggests that depression can directly stimulate the production of pro-inflammatory cytokines [20], or inflammatory factors such as C-reactive proteins that influence a spectrum of conditions such as type 2 diabetes [12]. One of the hypothesized mechanisms is that high prefrontal glutamate levels may play an important role precipitating the depression presenting in diabetic patients [21].…”

Does severe hypoglycaemia disrupt academic achievement in children with early onset diabetes?

“…Hannonen et al's work points to higher blood glucose levels, particularly when they occur within the first year or so of diagnosis. We know that diabetic patients have higher brain glucose levels than their non-diabetic counterparts, 5 and we also know that glucose can have neurotoxic effects, 6 and so it is quite plausible that during key developmental periods, very high, rather than very low, blood glucose levels could lead to the structural and functional changes in the brain that are associated with early onset diabetes. 7 Managing diabetic patients at any age can be challenging, but when younger children are involved, it is critically important to ensure that blood glucose values neither fall too low, nor rise too high.…”

“…However, there was significant heterogeneity between trials. 5 Many individuals were entered into the studies at differing stages of their natural history, with wide age ranges. Further, inclusion criteria (and thereby definition of LGS) were not consistent across all studies; many only required a history of 'drop attacks' and the demonstration of slow spike wave in a recent EEG.…”